Background: Significant health disparities exist for Hispanics and Native Americans in screening and treatment for problem alcohol and opioid use in New Mexico. Despite the availability of methods for screening and brief intervention in primary care for problem alcohol use and opioid dependence, data continue to show that such strategies are underutilized. Improved alcohol and opioid services delivery in primary care will require innovative understandings of the community and primary care context in which these services are provided. Objectives and aims: The specific aims of this ecological, mixed method project are: 1) To more fully describe the complex factors influencing implementation of evidence-based screening and treatment for problem alcohol use and opioid dependence by conducting a three-phase mixed-method study in a primary care practice-based research network; 2) To more fully understand community level factors and perceptions of alcohol use, opioid dependence and the acceptance of screening and treatment for these problems in primary care; 3) Based upon Community and Primary Care Provider feedback, create flexible models for matching approaches to alcohol and opioid screening and intervention with different primary care and community settings; and 4) To assess the feasibility of these models in enhancing screening and intervention for problem alcohol and opioid use in primary care. Design and methods: A multi-method, three phase study is planned, using survey, qualitative case study, interview, and observational data to conduct up to 12 primary care clinic assessments from which a pilot intervention study will be developed and implemented. The study will be conducted in a primary care practice-based research network and will use a participatory approach to engage community behavioral health and substance use partners. Outcomes: This study will produce data that will be used to create and test the feasibility of new model(s) for intervening in primary care clinics to enhance alcohol abuse and opioid dependence services. In contrast to previous ideas about changing primary care clinic to increase attention to problem alcohol use and opioid dependency issues, these innovative models will incorporate the situational and complex nature of primary care. Subsequent research will aim to test the effectiveness of interventions based on the new model(s) on a broader scale aimed at reducing substance use disparities among Hispanics and Native Americans.